Rauh, Oliver ; Opper, Jennifer ; Sturm, Maximilian ; Drexler, Nils ; Scheub, Deborah D. ; Hansen, Ulf-Peter ; Thiel, Gerhard ; Schroeder, Indra (2022)
Role of ion distribution and energy barriers for concerted motion of subunits in selectivity filter gating of a K+ channel.
In: Journal of molecular biology, 434 (9)
doi: 10.1016/j.jmb.2022.167522
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

Most potassium channels have two main gate locations, hosting an inner gate at the cytosolic entrance and a filter gate in the selectivity filter; the function of these gates is in many channels coupled. To obtain exclusive insights into the molecular mechanisms that determine opening and closing of the filter gate, we use a combination of single-channel recordings and gating analysis in the minimal viral channel Kcv. This channel has no inner gate and its fast closing at negative voltages can therefore be entirely assigned to the filter gate. We find that mutations of S42 in the pore helix severely slow down closing of this filter gate, an effect which is not correlated with hydrogen bond formation by the amino acid at this position. Hence, different from KcsA, which contains the critical E71 in the equivalent position forming a salt bridge, the coupling between selectivity filter and surrounding structures for filter gating must in Kcv rely on different modes of interaction. Quantitative analysis of concatemers carrying different numbers of S42T mutations reveals that each subunit contributes the same amount of ∼0.4 kcal/mol to the energy barrier for filter closure indicating a concerted action of the subunits. Since the mutations have neither an influence on the unitary current nor on the voltage dependency of the gate, the data stress that the high subunit cooperativity is mediated through conformational changes rather than through changes in the ion occupation in the selectivity filter. - 240 words.

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